We chose carvedilol for several reasons: (i) it is among the most effective β-blockers for improving survival after myocardial infarction22,23, (ii) it is one out of four β-blockers approved for the treatment of heart failure but the only one in this subgroup with β2-ISA24 and (iii) it is frequently presented and used as a prototype to portray a paradigmatic signalling mechanism: G protein-independent, arrestin-dependent signalling, also known as arrestin-biased signalling25,26. This evidence concerns the gene SAG and heart failure.